LDAH_MOUSE
ID LDAH_MOUSE Reviewed; 326 AA.
AC Q8BVA5; Q3TRE7; Q5RL52; Q6PG15; Q8BVV0;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 25-MAY-2022, entry version 122.
DE RecName: Full=Lipid droplet-associated hydrolase;
DE EC=3.1.1.- {ECO:0000305|PubMed:24357060};
DE AltName: Full=Lipid droplet-associated serine hydrolase {ECO:0000303|PubMed:24357060};
DE Short=mLDAH {ECO:0000303|PubMed:24357060};
GN Name=Ldah {ECO:0000303|PubMed:24357060};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3 AND 4).
RC STRAIN=C57BL/6J; TISSUE=Diencephalon, Head, and Hypothalamus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J, and FVB/N; TISSUE=Brain, and Colon;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Liver, Lung, Pancreas, and
RC Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=23525007; DOI=10.1242/jcs.120493;
RA Thiel K., Heier C., Haberl V., Thul P.J., Oberer M., Lass A., Jackle H.,
RA Beller M.;
RT "The evolutionarily conserved protein CG9186 is associated with lipid
RT droplets, required for their positioning and for fat storage.";
RL J. Cell Sci. 126:2198-2212(2013).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, IDENTIFICATION BY MASS SPECTROMETRY,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF SER-140.
RX PubMed=24357060; DOI=10.1161/atvbaha.113.302448;
RA Goo Y.H., Son S.H., Kreienberg P.B., Paul A.;
RT "Novel lipid droplet-associated serine hydrolase regulates macrophage
RT cholesterol mobilization.";
RL Arterioscler. Thromb. Vasc. Biol. 34:386-396(2014).
RN [6]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=27836991; DOI=10.1194/jlr.m072538;
RA Kory N., Grond S., Kamat S.S., Li Z., Krahmer N., Chitraju C., Zhou P.,
RA Froehlich F., Semova I., Ejsing C., Zechner R., Cravatt B.F.,
RA Farese R.V. Jr., Walther T.C.;
RT "Mice lacking lipid droplet-associated hydrolase, a gene linked to human
RT prostate cancer, have normal cholesterol ester metabolism.";
RL J. Lipid Res. 58:226-235(2017).
CC -!- FUNCTION: Probable serine lipid hydrolase associated with lipid
CC droplets (PubMed:24357060). Appears to lack cholesterol esterase
CC activity (PubMed:24357060, PubMed:27836991). Appears to lack
CC triglyceride lipase activity (PubMed:23525007, PubMed:24357060,
CC PubMed:27836991). Highly expressed in macrophage-rich areas in
CC atherosclerotic lesions, suggesting that it could promote cholesterol
CC ester turnover in macrophages (PubMed:24357060).
CC {ECO:0000269|PubMed:23525007, ECO:0000269|PubMed:24357060,
CC ECO:0000269|PubMed:27836991}.
CC -!- SUBCELLULAR LOCATION: Lipid droplet {ECO:0000269|PubMed:23525007,
CC ECO:0000269|PubMed:24357060}. Endoplasmic reticulum
CC {ECO:0000269|PubMed:23525007}. Note=Localizes to the endoplasmic
CC reticulum in absence of lipid droplets and translocates to lipid
CC droplets upon lipid storage induction. {ECO:0000269|PubMed:23525007}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q8BVA5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8BVA5-2; Sequence=VSP_027797;
CC Name=3;
CC IsoId=Q8BVA5-3; Sequence=VSP_027796;
CC Name=4;
CC IsoId=Q8BVA5-4; Sequence=VSP_027796, VSP_027798, VSP_027799;
CC -!- TISSUE SPECIFICITY: Expressed in liver, adrenal gland, prostate,
CC spleen, kidney, brown and white adipose tissue, testis and to a lesser
CC extent in brain (at protein level) (PubMed:27836991). Expressed in bone
CC marrow-derived macrophages (at protein level) (PubMed:27836991).
CC Expressed in heart (PubMed:27836991). Highly expressed in macrophage-
CC rich areas in atherosclerotic lesions (PubMed:24357060).
CC {ECO:0000269|PubMed:24357060, ECO:0000269|PubMed:27836991}.
CC -!- DISRUPTION PHENOTYPE: Mice have no obvious defects (PubMed:27836991).
CC Size of adipocytes is normal (PubMed:27836991). Lipid metabolism is
CC normal (PubMed:27836991). Cholesterol ester turnover or hydrolysis in
CC bone marrow macrophages, brown adipose tissue or liver is normal
CC (PubMed:27836991). No defect in body composition, energy expenditure,
CC locomotor activity, water or food intake, respiratory exchange ratio,
CC oxygen consumption, carbon dioxide production or glucose homeostasis
CC (PubMed:27836991). {ECO:0000269|PubMed:27836991}.
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. LDAH family.
CC {ECO:0000305}.
CC -!- CAUTION: The catalytic activity is unsure despite catalytic sites being
CC conserved (PubMed:23525007, PubMed:27836991). One report shows that
CC LDAH has low cholesterol esterase activity when overexpressed in RAW
CC 264.7 macrophages (PubMed:24357060). However, in another study, LDAH
CC lacks cholesterol esterase activity when overexpressed in Hela cells
CC (PubMed:27836991). Lack lipolytic activity towards trioleoylglycerol,
CC dioleoylglycerol or monooleoylglycerol when overexpressed in COS-7
CC cells or Hela cells (PubMed:23525007, PubMed:27836991).
CC {ECO:0000269|PubMed:23525007, ECO:0000269|PubMed:24357060,
CC ECO:0000269|PubMed:27836991}.
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DR EMBL; AK076460; BAC36352.1; -; mRNA.
DR EMBL; AK079099; BAC37539.1; -; mRNA.
DR EMBL; AK162850; BAE37083.1; -; mRNA.
DR EMBL; BC046986; AAH46986.1; -; mRNA.
DR EMBL; BC057311; AAH57311.1; -; mRNA.
DR CCDS; CCDS25798.1; -. [Q8BVA5-1]
DR CCDS; CCDS49023.1; -. [Q8BVA5-2]
DR RefSeq; NP_001161239.1; NM_001167767.1.
DR RefSeq; NP_765989.3; NM_172401.4.
DR RefSeq; XP_006515263.2; XM_006515200.2.
DR RefSeq; XP_006515267.1; XM_006515204.2.
DR AlphaFoldDB; Q8BVA5; -.
DR BioGRID; 213072; 1.
DR STRING; 10090.ENSMUSP00000042285; -.
DR ESTHER; mouse-Ldah; LIDHydrolase.
DR iPTMnet; Q8BVA5; -.
DR PhosphoSitePlus; Q8BVA5; -.
DR SwissPalm; Q8BVA5; -.
DR EPD; Q8BVA5; -.
DR jPOST; Q8BVA5; -.
DR MaxQB; Q8BVA5; -.
DR PaxDb; Q8BVA5; -.
DR PeptideAtlas; Q8BVA5; -.
DR PRIDE; Q8BVA5; -.
DR ProteomicsDB; 264918; -. [Q8BVA5-1]
DR ProteomicsDB; 264919; -. [Q8BVA5-2]
DR ProteomicsDB; 264920; -. [Q8BVA5-3]
DR ProteomicsDB; 264921; -. [Q8BVA5-4]
DR DNASU; 68832; -.
DR GeneID; 68832; -.
DR KEGG; mmu:68832; -.
DR UCSC; uc007mzg.2; mouse. [Q8BVA5-1]
DR UCSC; uc007mzk.2; mouse. [Q8BVA5-3]
DR CTD; 60526; -.
DR MGI; MGI:1916082; Ldah.
DR eggNOG; KOG3975; Eukaryota.
DR InParanoid; Q8BVA5; -.
DR OrthoDB; 1163030at2759; -.
DR PhylomeDB; Q8BVA5; -.
DR TreeFam; TF313050; -.
DR BioGRID-ORCS; 68832; 0 hits in 71 CRISPR screens.
DR ChiTaRS; Ldah; mouse.
DR PRO; PR:Q8BVA5; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q8BVA5; protein.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005811; C:lipid droplet; IDA:UniProtKB.
DR GO; GO:0004771; F:sterol esterase activity; IDA:UniProtKB.
DR GO; GO:0090077; P:foam cell differentiation; TAS:UniProtKB.
DR GO; GO:0019915; P:lipid storage; IBA:GO_Central.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR019363; LDAH.
DR PANTHER; PTHR13390; PTHR13390; 1.
DR Pfam; PF10230; LIDHydrolase; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
DR PROSITE; PS00120; LIPASE_SER; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Endoplasmic reticulum; Hydrolase; Lipid droplet;
KW Reference proteome.
FT CHAIN 1..326
FT /note="Lipid droplet-associated hydrolase"
FT /id="PRO_0000300125"
FT ACT_SITE 140
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10037"
FT ACT_SITE 272
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:Q9H6V9"
FT ACT_SITE 301
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:Q9H6V9"
FT VAR_SEQ 1..170
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_027796"
FT VAR_SEQ 237..326
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_027797"
FT VAR_SEQ 264..270
FT /note="LKFYYGK -> EGNSTLP (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_027798"
FT VAR_SEQ 271..326
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_027799"
FT MUTAGEN 140
FT /note="S->C: Abolishes active hydrolase probe binding in
FT serine hydrolase assays."
FT /evidence="ECO:0000269|PubMed:24357060"
FT CONFLICT 154
FT /note="L -> P (in Ref. 2; AAH46986/AAH57311)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 326 AA; 37374 MW; EE979E9FB9FA9C28 CRC64;
MASEVEEQIP VREEFFLCGG VETKIIKCGP WTNLFEKQDV SKPKQLIFII PGNPGYSAFY
VPFAKALYTL MKSRFPVWII SHAGFSVTPK DKKVLAAPQE ESNAQKIEDV YGLNGQIEHK
IAFLRAHVPK DVKLILIGHS VGTYMTLHVM KRVLELPVAH AFLLFPTIER MSESPNGKFA
TPFLCQFRYL LYATSYLLFK PCPEVIKSFI IQKLMGQMNI KLELPLTDIL QPFCLANAAY
LGSQEMVQIV KRDDDIIKEF LPKLKFYYGK TDGWCPVKYY EDMKKDFPEG NIYLCEKGIP
HAFVLDFSQE MATIVAEWIN NRPPRK
